Updated consensus algorithm no longer includes rosiglitazone as recommended diabetes therapy

Guidelines still recommend lifestyle intervention, metformin as first-line therapy.

A panel of experts convened by the American Diabetes Association and European Association for the Study of Diabetes has issued updated treatment recommendations for the management of hyperglycemia in type 2 diabetes.

The algorithm was updated from when it was first published in 2006.

“The major premises of the revised consensus algorithm remain true to the original version,” David M. Nathan, MD, chair of the consensus committee, told Endocrine Today. The algorithm still recommends aggressive lifestyle intervention and metformin as first-line therapy for all patients with HbA1c ≥7% and changes in therapy every three months to reach optimal glycemic control.

However, notable changes included “downgrading the thiazolidinediones as a class of drugs to the second tier and eliminating rosiglitazone from our recommended medications,” Nathan said.

In addition, exenatide (Byetta; Amylin, Lilly) and pioglitazone are now recommended as possible second-tier therapies for patients at risk for severe hypoglycemia.

The updated consensus algorithm for the initiation and adjustment of diabetes therapy was published online in Diabetes Care and Diabetologia.

New stepped-care treatment approach

“Not only were new drug classes FDA approved since the last iteration of the consensus algorithm, but there were more clinical data available on the glycemic targets, cardiovascular outcomes of intensive therapy and glycemic results of several drug classes. The accumulating evidence prompted the consensus committee to reexamine the original algorithm,” said Nathan, director of the General Clinical Research Center and Diabetes Center at Massachusetts General Hospital and professor of medicine at Harvard Medical School.

If glucose and HbA1c goals are not reached or maintained with lifestyle change and metformin alone, the algorithm recommends progression to step two: addition of basal insulin or sulfonylurea as the preferred, well-validated route. The less well-validated route includes addition of pioglitazone or glucagon-like peptide 1 agonist as the second step, according to Nathan.

However, the authors suggested that pioglitazone or GLP-1 agonists be used only in selected clinical settings, such as in patients in whom hypoglycemia is particularly undesirable.

If the step-two therapies do not maintain glucose and HbA1c goals, the authors suggested progression to step three: basal insulin and then transition to intensive insulin, if needed.

Amylin agonists, alpha-glucosidase inhibitors, glinides and DPP-IV inhibitors were not included in the list of preferred agents in this algorithm.

“These choices are based on their effectiveness in lowering glycemia, safety, tolerability, ease of use and cost. We tried to simplify the format of the algorithm to make it more easily accessible for practitioners,” Nathan said. – by Katie Kalvaitis

Diabetes Care. 2008;doi:10.2337/dc08-9025.

Diabetologia. 2008;doi:10.1007/s00125-008-1157-y.

In an article purporting to offer new approaches to the treatment of type 2 diabetes, Nathan and colleagues offer many incorrect observations pertaining to approaches to the topic. The authors appropriately suggest that less expensive medications are preferable to more expensive ones, all things being equal, but then reiterate the assertion that the older medicines are more potent in glucose lowering, failing to understand that because these agents were studied at a time when it was considered ethical to treat less aggressively the trials of their efficacy showed greater glucose- and HbA1c-lowering, which we now realize to be simply a function of the crucial dependence of the degree of such reductions on baseline glycemia. The authors fail to include important agents such as the alpha glucosidase inhibitors and DPP-IV inhibitors in their algorithm, despite important studies showing efficacy and safety of these agents. Finally, the authors dismiss rosiglitazone as an effective TZD, apparently considering the methodologically flawed meta-analysis by Steven E. Nissen, MD, and Kathy Wolski, MPH, to have been correct in finding it to increase macrovascular disease risk, despite the numerous subsequent studies which have shown that with appropriate statistical analysis the assertion is found incorrect.

– Zachary T. Bloomgarden, MD

Endocrine Today Editorial Board member